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2.
ABCS health sci ; 46: e021203, 09 fev. 2021. tab
Artículo en Inglés | LILACS | ID: biblio-1147180

RESUMEN

INTRODUCTION: The resistance of fungal species to drugs usually used in clinics is of great interest in the medical field. OBJECTIVE: To evaluate susceptibility and in vitro response of species of Trichophyton spp. to antifungal drugs of interest in clinical medicine. METHODS: 12 samples of clinical isolates from humans were used, nine of T. mentagrophytes and three of T. tonsurans. Susceptibility tests were performed according to the agar diffusion (AD) and broth microdilution (BM) methods. RESULTS: In the AD method, the species T. tonsurans presented a percentage of sensitivity of 33% in relation to amphotericin B and 66% to itraconazole, with 100% resistance to ketoconazole and fluconazole. T. mentagrophytes also showed 100% resistance to ketoconazole in this technique, with 11% sensitivity to ketoconazole, 22% to itraconazole and 22% of samples classified as sensitive dose dependent. In the MC method, the species T. tonsurans presented a sensitivity percentage of 66%, 55% and 33% in relation to ketoconazole, fluconazole and itraconazole, respectively. The T. mentagrophytes species presented sensitivity percentages of 11%, 11%, 33% and 55% for amphotericin B, itraconazole, ketoconazole and fluconazole, respectively. CONCLUSION: There was resistance in vitro of the species of T. mentagrophytes and T. tonsurans against the antifungal fluconazole and relative resistance against ketoconazole in the AD method. In BM, however, important percentages of sensitivity were observed for the two species analyzed in relation to the antifungals fluconazole and ketoconazole when compared to itraconazole and amphotericin B.


INTRODUÇÃO: A resistência de espécies fúngicas às drogas usualmente empregadas no meio clínico é motivo de grande interesse na área médica. OBJETIVO: Avaliar susceptibilidade e resposta in vitro de espécies de Trichophyton spp. a drogas antifúngicas de interesse em clínica médica. MÉTODOS: Foram utilizadas 12 amostras de isolados clínicos de humanos, sendo nove de T. mentagrophytes e três de T. tonsurans. Foram realizados testes de susceptibilidade segundo os métodos de difusão em ágar (DA) e microdiluição em caldo (MC). RESULTADOS: No método de DA, a espécie T. tonsurans apresentou percentual de sensibilidade de 33% em relação à anfotericina B e de 66% ao itraconazol, com 100% de resistência frente ao cetoconazol e ao fluconazol. A espécie T. mentagrophytes também apresentou 100% de resistência frente ao cetoconazol nesta técnica, com 11% de sensibilidade ao cetoconazol, 22% ao itraconazol e 22% das amostras classificadas como sensível dose dependente. No método de MC, a espécie T. tonsurans apresentou percentual de sensibilidade de 66%, 55% e 33% em relação ao cetoconazol, fluconazol e itraconazol, respectivamente. A espécie T. mentagrophytes apresentou percentuais de sensibilidade de 11%, 11%, 33% e 55% para anfotericina B, itraconazol, cetoconazol e fluconazol, respectivamente. CONCLUSÃO: Houve resistência in vitro das espécies do T. mentagrophytes e T. tonsurans frente ao antifúngico fluconazol e resistência relativa frente ao cetoconazol no método de DA. Na MC, no entanto, foram observados importantes percentuais de sensibilidade das duas espécies analisadas frente aos antifúngicos fluconazol e cetoconazol quando comparadas ao itraconazol e à anfotericina B.


Asunto(s)
Trichophyton/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica , Susceptibilidad a Enfermedades/microbiología , Antifúngicos/farmacología , Tiña/microbiología , Tiña/tratamiento farmacológico , Recuento de Colonia Microbiana , Fluconazol/farmacología , Anfotericina B/farmacología , Itraconazol/farmacología , Cetoconazol/farmacología
3.
J Insect Sci ; 21(1)2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33560356

RESUMEN

Honey bees are important pollinators of wild plants and crops. MicroRNAs (miRNAs) are endogenous regulators of gene expression. In this study, we initially determined that the lethal concentration 50 (LC50) of dinotefuran was 0.773 mg/l. Then, the expression profiles and differentially expressed miRNAs (DE miRNAs) in honey bee brains after 1, 5, and 10 d of treatment with the lethal concentration 10 (LC10) of dinotefuran were explored via deep small-RNA sequencing and bioinformatics. In total, 2, 23, and 27 DE miRNAs were identified after persistent exposure to the LC10 of dinotefuran for 1, 5, and 10 d, respectively. Some abundant miRNAs, such as ame-miR-375-3p, ame-miR-281-5p, ame-miR-3786-3p, ame-miR-10-5p, and ame-miR-6037-3p, were extremely significantly differentially expressed. Enrichment analysis suggested that the candidate target genes of the DE miRNAs are involved in the regulation of biological processes, cellular processes, and behaviors. These results expand our understanding of the regulatory roles of miRNAs in honey bee Apis mellifera (Hymenopptera: Apidae) responses to neonicotinoid insecticides and facilitate further studies on the functions of miRNAs in honey bees.


Asunto(s)
Abejas/efectos de los fármacos , Encéfalo/metabolismo , Guanidinas/toxicidad , Insecticidas/toxicidad , MicroARNs/genética , Neonicotinoides/toxicidad , Nitrocompuestos/toxicidad , Transcriptoma , Animales , Abejas/genética , Abejas/metabolismo , Encéfalo/efectos de los fármacos , MicroARNs/metabolismo
4.
J Insect Sci ; 21(1)2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33560359

RESUMEN

The interest in using byproducts from agro-food industries as a rearing substrate for insects is increasing rapidly. We investigated the influence of byproducts of vegetal origin (okara-a byproduct of soy milk production, maize distillers with solubles, brewer's grains), used as rearing diet for black soldier fly larvae (BSFL), on the following parameters: biomass production, substrate reduction (SR), nutritional profile and in vitro digestibility, and larval gut microbiota. Hen diet was used as a control substrate. The highest larval biomass was collected on maize distillers, whereas the highest SR was observed on okara. The rearing substrate affected ash, ether extract, and chitin larval content. The BSFL reared on okara were characterized by a lower lauric acid content (17.6% of total fatty acids). Diets also influenced in vitro crude protein digestibility (%) for monogastrics, with the highest values for BSFL reared on maize distillers (87.8), intermediate for brewer's grains and okara BSFL, and the lowest for hen BSFL (82.7). The nutritive value for ruminants showed a lower Net Energy for lactation for BSFL reared on hen diet than okara and dried maize distillers BSFL. The different byproducts showed an influence on the larval gut microbiota, with a major bacterial complexity observed on larvae fed with the hen diet. The neutral detergent fiber concentration of dietary substrate was negatively correlated with Firmicutes and Actinobacteria relative abundance. Insects valorized byproducts converting them into high-value larval biomass to be used for feed production. The results evidenced the effects of the tested byproducts on the measured parameters, underling the chemical composition importance on the final insect meal quality.


Asunto(s)
Agricultura , Digestión , Dípteros/fisiología , Residuos Industriales/análisis , Microbiota , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Digestión/efectos de los fármacos , Dípteros/química , Dípteros/crecimiento & desarrollo , Dípteros/microbiología , Larva/química , Larva/crecimiento & desarrollo , Larva/microbiología , Larva/fisiología , Microbiota/efectos de los fármacos
5.
Mo Med ; 118(1): 68-73, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551489

RESUMEN

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immune system has been known for decades, the benefits of magnesium has only recently been elucidated. Indeed, magnesium is important for activating vitamin D and has a protective role against oxidative stress. Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation. Furthermore, magnesium deficient animals and humans have depressed immune responses, which, when supplemented with magnesium, a partial or near full reversal of the immunodeficiency occurs. Moreover, intracellular free magnesium levels in natural killer cells and CD8 killer T cells regulates their cytotoxicity. Considering that magnesium and vitamin D are important for immune function and cellular resilience, a deficiency in either may contribute to cytokine storm in the novel coronavirus 2019 (COVID-19) infection.


Asunto(s)
/complicaciones , Síndrome de Liberación de Citoquinas/etiología , Coagulación Intravascular Diseminada/etiología , Enfermedades del Sistema Inmune/etiología , Deficiencia de Magnesio/complicaciones , Deficiencia de Vitamina D/complicaciones , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , /tratamiento farmacológico , Humanos , Células Asesinas Naturales/efectos de los fármacos , Magnesio/administración & dosificación , Magnesio/farmacología , Magnesio/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , /genética , Vitamina D/administración & dosificación , Vitamina D/farmacología , Vitamina D/uso terapéutico , Vitaminas/administración & dosificación , Vitaminas/farmacología , Vitaminas/uso terapéutico
8.
Sci Rep ; 11(1): 3379, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33564039

RESUMEN

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a pandemic throughout 2020. Since the virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry, increment of ACE2 would lead to an increased risk of SARS-CoV-2 infection. At the same time, an association of the ABO blood group system with COVID-19 has also been highlighted: there is increasing evidence to suggest that non-O individuals are at higher risk of severe COVID-19 than O individuals. These findings imply that simultaneous suppression of ACE2 and ABO would be a promising approach for prevention or treatment of COVID-19. Notably, we have previously clarified that histone deacetylase inhibitors (HDACIs) are able to suppress ABO expression in vitro. Against this background, we further evaluated the effect of HDACIs on cultured epithelial cell lines, and found that HDACIs suppress both ACE2 and ABO expression simultaneously. Furthermore, the amount of ACE2 protein was shown to be decreased by one of the clinically-used HDACIs, panobinostat, which has been reported to reduce B-antigens on cell surfaces. On the basis of these findings, we conclude that panobinostat could have the potential to serve as a preventive drug against COVID-19.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Panobinostat/farmacología , Ácido Butírico/farmacología , /prevención & control , Línea Celular , Células Epiteliales/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Serina Endopeptidasas
10.
Nat Commun ; 12(1): 1054, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594052

RESUMEN

In acute myeloid leukemia (AML), molecular heterogeneity across patients constitutes a major challenge for prognosis and therapy. AML with NPM1 mutation is a distinct genetic entity in the revised World Health Organization classification. However, differing patterns of co-mutation and response to therapy within this group necessitate further stratification. Here we report two distinct subtypes within NPM1 mutated AML patients, which we label as primitive and committed based on the respective presence or absence of a stem cell signature. Using gene expression (RNA-seq), epigenomic (ATAC-seq) and immunophenotyping (CyToF) analysis, we associate each subtype with specific molecular characteristics, disease differentiation state and patient survival. Using ex vivo drug sensitivity profiling, we show a differential drug response of the subtypes to specific kinase inhibitors, irrespective of the FLT3-ITD status. Differential drug responses of the primitive and committed subtype are validated in an independent AML cohort. Our results highlight heterogeneity among NPM1 mutated AML patient samples based on stemness and suggest that the addition of kinase inhibitors to the treatment of cases with the primitive signature, lacking FLT3-ITD, could have therapeutic benefit.


Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación/genética , Proteínas Nucleares/genética , Cromatina/metabolismo , Análisis por Conglomerados , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunofenotipificación , Fenotipo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Reproducibilidad de los Resultados , Análisis de Supervivencia
11.
Nat Commun ; 12(1): 1055, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594058

RESUMEN

mTORC1, a central controller of cell proliferation in response to growth factors and nutrients, is dysregulated in cancer. Whereas arginine activates mTORC1, it is overridden by high expression of cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1). Because cancer cells often encounter low levels of nutrients, an alternative mechanism might exist to regulate CASTOR1 expression. Here we show K29-linked polyubiquitination and degradation of CASTOR1 by E3 ubiquitin ligase RNF167. Furthermore, AKT phosphorylates CASTOR1 at S14, significantly increasing its binding to RNF167, and hence its ubiquitination and degradation, while simultaneously decreasing its affinity to MIOS, leading to mTORC1 activation. Therefore, AKT activates mTORC1 through both TSC2- and CASTOR1-dependent pathways. Several cell types with high CASTOR1 expression are insensitive to arginine regulation. Significantly, AKT and RNF167-mediated CASTOR1 degradation activates mTORC1 independent of arginine and promotes breast cancer progression. These results illustrate a mTORC1 regulating mechanism and identify RNF167 as a therapeutic target for mTORC1-dysregulated diseases.


Asunto(s)
Carcinogénesis/metabolismo , Carcinogénesis/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Proteolisis , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Animales , Arginina/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Péptidos y Proteínas de Señalización Intercelular/farmacología , Cinética , Lisina/metabolismo , Ratones Desnudos , Fosforilación/efectos de los fármacos , Proteolisis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ubiquitinación/efectos de los fármacos
12.
Nat Commun ; 12(1): 1068, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594066

RESUMEN

A graphdiyne-based artificial synapse (GAS), exhibiting intrinsic short-term plasticity, has been proposed to mimic biological signal transmission behavior. The impulse response of the GAS has been reduced to several millivolts with competitive femtowatt-level consumption, exceeding the biological level by orders of magnitude. Most importantly, the GAS is capable of parallelly processing signals transmitted from multiple pre-neurons and therefore realizing dynamic logic and spatiotemporal rules. It is also found that the GAS is thermally stable (at 353 K) and environmentally stable (in a relative humidity up to 35%). Our artificial efferent nerve, connecting the GAS with artificial muscles, has been demonstrated to complete the information integration of pre-neurons and the information output of motor neurons, which is advantageous for coalescing multiple sensory feedbacks and reacting to events. Our synaptic element has potential applications in bioinspired peripheral nervous systems of soft electronics, neurorobotics, and biohybrid systems of brain-computer interfaces.


Asunto(s)
Grafito/farmacología , Neuronas Eferentes/fisiología , Sinapsis/fisiología , Dendritas/efectos de los fármacos , Dendritas/fisiología , Teoría Funcional de la Densidad , Difusión , Iones , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Plasticidad Neuronal , Neuronas Eferentes/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Temperatura
13.
Nat Commun ; 12(1): 1065, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594067

RESUMEN

The production of blood cells during steady-state and increased demand depends on the regulation of hematopoietic stem cell (HSC) self-renewal and differentiation. Similarly, the balance between self-renewal and differentiation of leukemia stem cells (LSCs) is crucial in the pathogenesis of leukemia. Here, we document that the TNF receptor superfamily member lymphotoxin-ß receptor (LTßR) and its ligand LIGHT regulate quiescence and self-renewal of murine and human HSCs and LSCs. Cell-autonomous LIGHT/LTßR signaling on HSCs reduces cell cycling, promotes symmetric cell division and prevents primitive HSCs from exhaustion in serial re-transplantation experiments and genotoxic stress. LTßR deficiency reduces the numbers of LSCs and prolongs survival in a murine chronic myeloid leukemia (CML) model. Similarly, LIGHT/LTßR signaling in human G-CSF mobilized HSCs and human LSCs results in increased colony forming capacity in vitro. Thus, our results define LIGHT/LTßR signaling as an important pathway in the regulation of the self-renewal of HSCs and LSCs.


Asunto(s)
Diferenciación Celular , Autorrenovación de las Células , Células Madre Hematopoyéticas/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Receptor beta de Linfotoxina/metabolismo , Células Madre Neoplásicas/patología , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Animales , Antígenos CD34/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Autorrenovación de las Células/efectos de los fármacos , Autorrenovación de las Células/genética , Daño del ADN , Fluorouracilo/farmacología , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos
14.
Nat Commun ; 12(1): 1052, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594070

RESUMEN

The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.


Asunto(s)
Glucólisis/efectos de los fármacos , Fosfofructoquinasas/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Trypanosoma/enzimología , Tripanosomiasis Africana/metabolismo , Tripanosomiasis Africana/parasitología , Enfermedad Aguda , Regulación Alostérica/efectos de los fármacos , Animales , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Estimación de Kaplan-Meier , Ratones , Parásitos/efectos de los fármacos , Fosfofructoquinasas/química , Fosfofructoquinasas/metabolismo , Unión Proteica/efectos de los fármacos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Multimerización de Proteína , Relación Estructura-Actividad , Trypanosoma/efectos de los fármacos , Tripanosomiasis Africana/tratamiento farmacológico
15.
Nat Commun ; 12(1): 1051, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594068

RESUMEN

In metabolic engineering, loss-of-function experiments are used to understand and optimise metabolism. A conditional gene inactivation tool is required when gene deletion is lethal or detrimental to growth. Here, we exploit auxin-inducible protein degradation as a metabolic engineering approach in yeast. We demonstrate its effectiveness using terpenoid production. First, we target an essential prenyl-pyrophosphate metabolism protein, farnesyl pyrophosphate synthase (Erg20p). Degradation successfully redirects metabolic flux toward monoterpene (C10) production. Second, depleting hexokinase-2, a key protein in glucose signalling transduction, lifts glucose repression and boosts production of sesquiterpene (C15) nerolidol to 3.5 g L-1 in flask cultivation. Third, depleting acetyl-CoA carboxylase (Acc1p), another essential protein, delivers growth arrest without diminishing production capacity in nerolidol-producing yeast, providing a strategy to decouple growth and production. These studies demonstrate auxin-mediated protein degradation as an advanced tool for metabolic engineering. It also has potential for broader metabolic perturbation studies to better understand metabolism.


Asunto(s)
Ácidos Indolacéticos/farmacología , Ingeniería Metabólica , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Terpenos/metabolismo , Proteínas Bacterianas/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Coenzima A Ligasas/metabolismo , Glucosa/metabolismo , Hexoquinasa/metabolismo , Limoneno/metabolismo , Análisis de Flujos Metabólicos , Fosfatos de Poliisoprenilo/metabolismo , Proteolisis/efectos de los fármacos , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/crecimiento & desarrollo , Sesquiterpenos/metabolismo
16.
Nat Commun ; 12(1): 1067, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594081

RESUMEN

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.


Asunto(s)
Inflamación/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Glicoproteínas de Membrana/metabolismo , Células Acinares/metabolismo , Células Acinares/patología , Animales , Colitis/metabolismo , Colitis/patología , Citocinas/metabolismo , Sulfato de Dextran , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Heces , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Inmunoglobulina A/metabolismo , Mucosa Intestinal/microbiología , Ratones Endogámicos C57BL , Páncreas/patología , Proteínas Recombinantes/farmacología , Factores de Transcripción/metabolismo , Regulación hacia Arriba/genética
17.
Rev Bras Parasitol Vet ; 30(1): e015920, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33605386

RESUMEN

The consumption of inadequately thermally treated fish is a public health risk due to the possible propagation of Anisakis larvae. The present study demonstrated the physiological and histopathological changes that accompanied an oral inoculation of crude extracts from fresh and thermally treated Anisakis Type II (L3) in rats. Worms were isolated from a marine fish and examined and identified using light and scanning electron microscopy. The study was performed in 6 rat groups: control (I), garlic oil (GO) inoculated (II), fresh L3 inoculated (III), thermally treated L3 inoculated (IV), fresh L3 + GO inoculated (V), and a thermally treated L3 + GO inoculated (VI) groups. Rats inoculated with fresh and thermally treated L3 showed abnormal liver and kidney functions associated with the destruction of normal architecture. GO produced a protective effect in rat groups inoculated with L3 extracts + GO via the amelioration of liver and kidney functions, which was confirmed by the marked normal structure on histology. Cooking of L3-infected fish induced severe alterations compared to uncooked fish. The administration of garlic before and after fish eating is recommended to avoid the dangerous effect of anisakids, even if they are cooked.


Asunto(s)
Compuestos Alílicos , Anisakiasis , Anisakis , Sulfuros , Compuestos Alílicos/farmacología , Compuestos Alílicos/uso terapéutico , Animales , Anisakiasis/tratamiento farmacológico , Anisakiasis/prevención & control , Anisakis/efectos de los fármacos , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Culinaria , Peces/parasitología , Parasitología de Alimentos , Larva , Ratas , Ratas Wistar , Sulfuros/farmacología , Sulfuros/uso terapéutico
18.
Rev Bras Parasitol Vet ; 30(1): e025220, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33605390

RESUMEN

Southern cattle tick resistance to pour-on and injectable acaricides has yet to be evaluated on a broader scope, and the paucity of information on the subject may hinder efforts to control this parasite. The objective of this study was to evaluate the resistance profile of ten populations of Rhipicephalus microplus to the acaricides fluazuron, fipronil and ivermectin in cattle herds in Mato Grosso do Sul, Brazil. The larval immersion test (LIT) was used to evaluate susceptibility to ivermectin and fipronil and the adult immersion test (AIT) was performed to evaluate fluazuron. Samples were randomly obtained in ten farms, and in general, we found resistance in five samples to fluazuron and in four samples to ivermectin and fipronil. Six samples showed incipient resistance to ivermectin and fipronil. Five of the ten evaluated samples showed resistance and/or incipient resistance to all the active ingredients, and the other five to two active ingredients. Among the samples classified as resistant, the average resistance ratio for ivermectin was 2.75 and 3.26 for fipronil. These results demonstrate the advanced status of resistance to the most modern chemical groups for the control of R. microplus in the state of Mato Grosso do Sul.


Asunto(s)
Acaricidas , Enfermedades de los Bovinos , Resistencia a Medicamentos , Rhipicephalus , Infestaciones por Garrapatas , Acaricidas/farmacología , Animales , Brasil , Bovinos , Enfermedades de los Bovinos/parasitología , Ivermectina/farmacología , Compuestos de Fenilurea/farmacología , Pirazoles/farmacología , Rhipicephalus/efectos de los fármacos , Infestaciones por Garrapatas/parasitología , Infestaciones por Garrapatas/veterinaria
19.
Int J Nanomedicine ; 16: 515-538, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33519199

RESUMEN

Background: Several studies have demonstrated various molecular mechanisms involved in the biogenesis and release of exosomes. However, how external stimuli, such as platinum nanoparticles (PtNPs), induces the biogenesis and release of exosomes remains unclear. To address this, PtNPs were synthesized using lutein to examine their effect on the biogenesis and release of exosomes in human lung epithelial adenocarcinoma cancer cells (A549). Methods: The size and concentration of isolated exosomes were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis system (NTA). Morphology and structure of exosomes were examined using scanning electron microscopy and transmission electron microscopy (TEM), respectively. Quantification of exosomes were analyzed by EXOCETTM assay and fluorescence polarization (FP). The expression of typical markers of exosomes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results: A549 cells cultured with PtNPs enhance exosome secretion by altering various physiological processes. Interestingly, A549 cells treated with PtNPs increases total protein concentration, biogenesis and release of exosomes associated with PtNPs-induced oxidative stress. GW4869 inhibits PtNPs induced biogenesis and release of exosomes and also acetylcholinesterase (AChE), neutral sphingomyelinase activity (n-SMase), and exosome counts. A549 cells pre-treated with N-acetylcysteine (NAC) significantly inhibited PtNPs induced exosome biogenesis and release. These findings confirmed that PtNPs-induced exosome release was due to the induction of oxidative stress and the ceramide pathway. These factors enhanced exosome biogenesis and release and may be useful in understanding the mechanism of exosome formation, release, and function. Conclusion: PtNPs provide a promising agent to increase exosome production in A549 cells. These findings offer novel strategies for enhancing exosome release, which can be applied in the treatment and prevention of cancer. Importantly, this is the first study, to our knowledge, showing that PtNPs stimulate exosome biogenesis by inducing oxidative stress and the ceramide pathway.


Asunto(s)
Adenocarcinoma del Pulmón/metabolismo , Ceramidas/metabolismo , Exosomas/metabolismo , Neoplasias Pulmonares/metabolismo , Nanopartículas del Metal/química , Estrés Oxidativo , Platino (Metal)/farmacología , Células A549 , Acetilcolinesterasa/metabolismo , Acetilcisteína/farmacología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Compuestos de Anilina/farmacología , Compuestos de Bencilideno/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Exosomas/ultraestructura , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Luteína/farmacología , Nanopartículas del Metal/ultraestructura , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , ARN Mensajero/genética , ARN Mensajero/metabolismo , Suero , Esfingomielina Fosfodiesterasa/metabolismo , Electricidad Estática
20.
Clin Appl Thromb Hemost ; 27: 1076029620983902, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33523711

RESUMEN

A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery. The aim of this study was to study the anticoagulant effects of dabigatran in patients with atrial fibrillation (AF) as assessed by the whole blood assays ROTEM, and how data from these methods correlate to plasma dabigatran concentrations measured by Hemoclot. ROTEM was performed with ROTEM Gamma (Pentapharm GmbH, Munich, Germany). The assays used in our study were Ex-tem and In-tem assay. Plasma dabigatran concentrations were determined by hemoclot thrombin inhibitor assay (Hyphen BioMed, France) at trough and post-dose in 27 patients on dabigatran 150 mg BID. Median plasma dabigatran concentrations at trough were 74 ng/mL (11.2-250) and post-dose (2 h after ingestion) 120 ng/mL (31-282). The ROTEM clotting time (CT) and maximum clot firmnes (MCF) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem (p < 0.0001) and In-tem (p < 0.0001). In summary, in our study, we have found that the ROTEM variable CT and MCF, when activated with triggers Ex-tem and In-tem, has a strong and highly significant correlation with the plasma dabigatran concentration in a real-life population of AF-patients and could thereby be an alternative to estimate dabigatran concentration in emergency situations. However, additional studies are needed to further validate these findings.


Asunto(s)
Antitrombinas/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Coagulación Sanguínea/efectos de los fármacos , Dabigatrán/uso terapéutico , Monitoreo de Drogas , Pruebas en el Punto de Atención , Tromboelastografía , Anciano , Anciano de 80 o más Años , Antitrombinas/sangre , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Dabigatrán/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Resultado del Tratamiento
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